A Longitudinal Study of COVID-19 Sequelae and Immunity
Authors: Laura C. Chambers, Francesca L. Beaudoin
Journal: Annals of Internal Medicine (2022)

Letters1 November 2022A Longitudinal Study of COVID-19 Sequelae and ImmunityFREELaura C. Chambers, PhD, MPH and Francesca L. Beaudoin, MD, PhD, MSLaura C. Chambers, PhD, MPHDepartment of Epidemiology and Long COVID Initiative, Brown University, Providence, Rhode Island (L.C.C., F.L.B.)Search for more papers by this author and Francesca L. Beaudoin, MD, PhD, MSDepartment of Epidemiology and Long COVID Initiative, Brown University, Providence, Rhode Island (L.C.C., F.L.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L22-0330 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: Sneller and colleagues' article (1) received controversial coverage on social media for the authors' conclusions that extensive diagnostic evaluation did not identify a cause of postacute sequelae of SARS-CoV-2 infection (PASC) and that persons with a history of anxiety disorder are at increased risk for PASC. Although we may be apt to dismiss such critiques in the age of misinformation, it is worth further examination lest we draw erroneous inferences about anxiety and PASC.The authors' primary analyses included 189 participants with a history of COVID-19 (104 with PASC and 85 without). Ignoring power lost because of (appropriate) correction of the false discovery rate, the study sample was sufficiently powered to detect an odds ratio of 4.6 (assuming 5% prevalence of the characteristic among control participants). An effect size of this magnitude is large and probably unreasonable given that PASC may represent multiple distinct conditions with different causes and risk factors. Exploratory immunologic and virologic evaluations included an even smaller subset of participants, further limiting power. The noted absence of associations may be true or simply due to limited power.Of note, the study measured prevalent PASC at study enrollment, which occurred approximately 5 months after COVID-19 onset. Given that some patients experience symptom resolution within 5 months (2), participants with resolved PASC at enrollment would have been misclassified as control participants “without PASC,” biasing results toward the null. The design was also subject to recall and selection bias that would have been mitigated with a prospective design or different sampling scheme. It is not surprising that persons with a history of anxiety who believed they had PASC might have been more apt to volunteer for a study about PASC. The authors acknowledge the limitations of self-referral, but it is also important to highlight how this sample differs from the general population. For example, 48% of participants had an advanced degree versus 13% of the U.S. population (3). Finally, analyses of risk factors for PASC were unadjusted, so associations may have been confounded by measured (such as female sex is associated with both PASC and anxiety disorders) and unmeasured (such as genetics) characteristics (4).This study contributes much-needed data on PASC and highlights critical areas for future research. However, we must not draw broad conclusions from a small study with important limitations, and appropriate messaging around the science is critical. Patients with PASC already experience stigma and difficulty accessing care (5); our early work on PASC should not exacerbate this.References1. Sneller MC, Liang CJ, Marques AR, et al. A longitudinal study of COVID-19 sequelae and immunity: baseline findings. Ann Intern Med. 2022;175:969-79. [PMID: 35605238] doi:10.7326/M21-4905 LinkGoogle Scholar2. UpToDate. Type, proportion, and duration of persistent COVID-19 symptoms. 2022. Accessed at www.uptodate.com/contents/image/print?imageKey=PULM%2F130356 on 7 July 2022. Google Scholar3. U.S. Census Bureau. Educational attainment in the United States: 2018 (Table 2). 2022. Accessed at www.census.gov/data/tables/2018/demo/education-attainment/cps-detailed-tables.html on 7 July 2022. Google Scholar4. DeMartini J, Patel G, Fancher TL. Generalized anxiety disorder. Ann Intern Med. 2019;170:ITC49-C64. [PMID: 30934083] doi:10.7326/AITC201904020 LinkGoogle Scholar5. Gorna R, MacDermott N, Rayner C, et al. Long COVID guidelines need to reflect lived experience. Lancet. 2021;397:455-7. [PMID: 33357467] doi:10.1016/S0140-6736(20)32705-7 CrossrefMedlineGoogle Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Department of Epidemiology and Long COVID Initiative, Brown University, Providence, Rhode Island (L.C.C., F.L.B.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L22-0330.This article was published at Annals.org on 1 November 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoA Longitudinal Study of COVID-19 Sequelae and Immunity: Baseline Findings Michael C. Sneller , C. Jason Liang , Adriana R. Marques , Joyce Y. Chung , Sujata M. Shanbhag , Joseph R. Fontana , Haniya Raza , Onyi Okeke , Robin L. Dewar , Bryan P. Higgins , Katie Tolstenko , Richard W. Kwan , Kathleen R. Gittens , Catherine A. Seamon , Genevieve McCormack , Jacob S. Shaw , Grace M. Okpali , Melissa Law , Krittin Trihemasava , Brooke D. Kennedy , Victoria Shi , J. Shawn Justement , Clarisa M. Buckner , Jana Blazkova , Susan Moir , Tae-Wook Chun , and H. Clifford Lane A Longitudinal Study of COVID-19 Sequelae and Immunity Michael C. Sneller , Adriana R. Marques , C. Jason Liang , and Joyce Y. Chung Metrics LatestKeywordsAnxietyCOVID-19MemoryPASCPsychiatry and mental healthQuality of lifeVaccines ePublished: 1 November 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.Loading ...